Management of catatonia in Parkinson’s disease with comorbid bipolar disorder: A case report and review of literature

Abstract

BACKGROUND

Non-motor symptoms are very common in Parkinson’s disease (PD) and can appear decades before motor symptoms. They occur at all stages of PD and may overshadow motor symptoms in advanced stages. These symptoms are disabling, reduce quality of life, and lead to early institutionalisation and increased caregiver burden. Bipolar disorder (BD) is less commonly reported but is more likely to be associated with PD compared to the general population. Patients with both BD and PD may occasionally develop catatonia.

CASE SUMMARY

This report describes the case of a 68-year-old with comorbid BD and PD who developed catatonia. He had type II BD with 2 hypomanic episodes and 5 episodes of severe, disabling, and poorly-responsive depression. The index depressive episode was chronic and severe, with anxiety, apathy, constipation, and urinary incontinence. Parkinsonian symptoms became evident during this episode, 30 years after the onset of BD. Lithium and levodopa led to some improvement, but were followed by worsening. He developed catatonic stupor within 3-4 days of adding quetiapine (75 mg/day) for depression. He had no sustained improvement after stopping quetiapine and adding lorazepam. However, there was a marked improvement in catatonic symptoms, depressive features, and parkinsonian symptoms with 6 treatments of electroconvulsive therapy (ECT). Subsequently, he received 6 continuation ECTs over 3 months. Continuation pharmacotherapy included mirtazapine and lithium, and levodopa for PD. He has remained asymptomatic for 18 months with this treatment.

CONCLUSION

ECT can lead to the resolution of catatonia and depressive symptoms, and improve motor symptoms in comorbid PD and BD.

Key Words: Parkinson’s disease; Non-motor symptoms; Bipolar disorder; Catatonia; Electroconvulsive therapy; Case report

Core Tip: Bipolar disorder (BD) is an infrequently reported but disabling non-motor manifestation of Parkinson’s disease (PD). The presentation of a 68-year-old man with comorbid BD and PD illustrates the comorbidity’s typical features, such as BD occurring in the pre-motor phase of PD, its association with anxiety, apathy, and other non-motor symptoms, and its poor prognosis. Catatonia is an uncommon manifestation of treatment-resistant depressive episodes in comorbid BD and PD. When benzodiazepines for catatonia fail, clinicians should actively consider electroconvulsive therapy. Close collaboration between psychiatrists and neurologists is essential for early detection and proper management of coexisting BD and PD with catatonia.

INTRODUCTION

Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder traditionally characterised by motor features such as rest tremors, muscular rigidity, and bradykinesia, along with postural instability and gait impairment in later stages[1-4]. The motor features are typically unilateral or asymmetrical and respond well to dopamine agonists, especially in the early stages. These motor symptoms result from dopamine deficiency caused by the loss of dopaminergic neurons and the deposition of Lewy bodies in the substantia nigra. Over the past two decades, there has been increasing recognition that PD includes both motor and non-motor symptoms, like sleep disturbances, sensory abnormalities, autonomic dysfunction, and psychiatric symptoms[4-6]. While dopamine deficiency in the substantia nigra causes motor symptoms, non-motor symptoms arise from Lewy body deposits in the autonomic, peripheral, and central nervous system sites beyond the basal ganglia[1-4,7]. These sites include the sympathetic ganglia of the gut and heart, the vagal and olfactory nuclei, the locus coeruleus, the raphe nuclei, the nucleus basalis, and brain regions such as the hypothalamus and limbic lobe. Moreover, multiple neurotransmitters, in addition to dopamine, are believed to be involved in the development of non-motor symptoms. Therefore, the current consensus is that PD is a multi-system, multi-organ neurodegenerative disorder comprising both motor and non-motor features. Psychiatric symptoms such as depression, cognitive impairment, anxiety, psychosis, apathy, and poor impulse control are among the most common non-motor symptoms of PD[8-12].

Non-motor symptoms of PD, particularly psychiatric abnormalities, negatively impact the course and outcome of PD, leading to increased disability, impaired quality of life, excess mortality, early institutionalisation, increased healthcare costs, and greater caregiver burden. Their prevalence increases over time, and in later stages of PD, they dominate the clinical presentation[1,2,5,7,13]. They are difficult to treat, although targeted treatment can reduce the associated disability. Despite their significance for the management of PD, non-motor symptoms are under-recognised and under-treated. Medical professionals, such as psychiatrists, neurologists, and other specialists, need to collaborate closely to manage non-motor symptoms of PD adequately.

Among all the psychiatric comorbidities of PD, bipolar disorder (BD) is the least studied condition. Comorbid PD and PD presenting with catatonia is also rare. This article describes the case of a 68-year-old man with BD and PD who developed catatonia. The clinical presentation highlights several features of comorbid BD and PD with catatonia. It also includes a focused review of non-motor symptoms of PD, including psychiatric comorbidities, and diagnosis and management of such complex presentations.

CASE PRESENTATION

Chief complaints

A 68-year-old man visited the outpatient psychiatric clinic at a large multi-speciality, tertiary-care hospital in northern India in August 2024. He was a retired insurance salesman living with his family in a town about 120 km away. He presented with depressive symptoms, slowness, and gait impairment.

History of present illness

The current (fifth) episode of depression began in November 2021. It was characterised by sadness, anhedonia, social withdrawal, low energy and fatigue, poor sleep and appetite, slowness, and feelings of low self-worth and hopelessness, along with excessive worrying, nervousness, anxiety, and agitation. He had received multiple antidepressants, antipsychotics, and mood stabilisers (quetiapine, valproate, and lithium) during this episode. However, he only experienced partial improvement and frequently worsened. From April 2023, when his depression was less severe, his family observed slowness, reduced interest, emotional indifference, stiffness, a shuffling gait with reduced arm movement, stooped posture, and handwriting difficulties. He lost interest in his surroundings and lacked initiative in his usual activities. He became unusually quiet and withdrawn with diminished emotional responsiveness. He was being treated for benign prostatic hypertrophy, but developed urinary incontinence in 2024. He also began experiencing constipation more often. However, the treating psychiatrist missed these features of PD and continued treatment with tianeptine, aripiprazole, and lithium. When he did not respond to this treatment, the treating psychiatrist referred the patient with a diagnosis of treatment-resistant BD.

History of past illness

He has had mental health issues since 1990, including two hypomanic episodes and four major depressive episodes. Although work-related stress triggered the depressive episodes, they were severe and disabling. Three of these episodes lasted between 9 and 16 months despite treatment with multiple antidepressants and mood stabilisers (quetiapine, valproate, and lamotrigine). In two episodes, he only recovered after receiving electroconvulsive therapy (ECT). The two hypomanic episodes occurred while he was on antidepressants and mood stabilisers, lasted approximately 3 months to 4 months, and caused little dysfunction.

There was no history of suicidal ideation, cognitive impairment, or substance abuse. The patient had been on treatment for hypertension and diabetes mellitus for the past 20 years. Other past medical issues included deep vein thrombosis and bilateral knee replacement for osteoporosis.

Personal and family history

There was no family history of mental illness. His birth, early development, education, work, and married life were unremarkable. He had some premorbid obsessive-compulsive traits.

Physical examination

During his first visit, family members showed a video of him bending over to open the door. Physical examination revealed bradykinesia, rigidity, a stooped posture, shuffling, a short-stepped gait, and reduced arm swing. The Movement Disorder Society Unified PD Rating Scale Part III-motor score was 57, suggesting moderate motor symptoms. He reported minimal depressive symptoms and was more distressed by urinary incontinence. Patient Health Questionnaire-9 score was 10, and the 24-item Hamilton Depression Rating Scale score was 9, indicating mild depression. Mini-Mental State Examination score was 29.

Laboratory examinations

All investigations were normal, apart from raised thyroid-stimulating hormone (11.9 μIU/mL) with normal thyroxine levels.

Imaging examinations

Magnetic resonance imaging of the brain showed age-related atrophy and small-vessel ischemic changes in the frontal and parietal lobes and in both basal ganglia.

MULTIDISCIPLINARY EXPERT CONSULTATION

Neurologists confirmed the diagnosis of PD and recommended levodopa 300 mg/day. Urologists advised catheterisation and solifenacin 5 mg/day for urinary problems. Endocrinologists started thyroxine 50 μg/day for subclinical hypothyroidism.

FINAL DIAGNOSIS

The initial diagnosis was PD and type II BD, with a current depressive episode in partial remission. The final diagnoses for this patient were type II BD, with the most recent episode being depression, idiopathic PD, and catatonia secondary to PD.

TREATMENT

Lithium 600 mg/day was continued (serum levels 0.63 mEq/L). There was a transient improvement in his depressive, anxiety, and parkinsonian symptoms, but they soon worsened. The psychiatric team started low-dose quetiapine (75 mg/day) for worsening depressive and anxiety symptoms.

OUTCOME AND FOLLOW-UP

Within 3-4 days of starting quetiapine, he developed catatonic features, including immobility, mutism, posturing, grimacing, rigidity, negativism, and refusal to eat or drink. The Bush-Francis Catatonia Rating Scale (BFCRS) score was 13. A lorazepam challenge test was positive, as the BFCRS scores decreased by greater than 50% with lorazepam (BFCRS 4). The treating team ruled out neuroleptic malignant syndrome because the International Consensus Criteria[14] score was 37, which was well below the cut-off of 74 (Supplementary Table 1). The treating team stopped quetiapine and started lorazepam 2 mg/day orally, but there was no sustained improvement. Subsequently, several injections of lorazepam 4 mg intravenously, 4-6 hourly, were tried for a day with no response and increased sedation.

His family gave written informed consent to start ECT. Acute ECT consisted of 6 bitemporal treatments on alternate days administered by a brief pulse machine. The ECT team titrated charges to estimate the seizure threshold and delivered ECT at 1.5 times the threshold. Anaesthetists used thiopentone sodium 200 mg for the induction and succinylcholine 100 mg for muscle relaxation. The charges varied from 347-551 milli-coulombs, and motor seizures ranged from 16-32 seconds. There was a marked improvement in catatonic symptoms (BFCRS 0), depressive features (Patient Health Questionnaire-nine item 1, Hamilton Depression Rating Scale score 1), and parkinsonian symptoms (Movement Disorder Society Unified PD Rating Scale 0), without any cognitive (Mini-Mental State Examination 30) or other adverse effects. Given the good response to acute ECT, the patient received 6 continuation ECT treatments over about 3 months. Cardiac abnormalities unrelated to ECT prevented further ECTs. He received continuation pharmacotherapy with mirtazapine 15 mg/day and lithium 450 mg/day (levels 0.57-0.72 mEq/L). A fluorodeoxyglucose positron emission tomography scan ruled out atypical PD. Parkinsonian symptoms improved further, and the neurologists reduced levodopa to 200 mg/day. His urinary symptoms also resolved, and the urologists removed his catheter and stopped solifenacin.

Over the past 18 months of follow-up, the patient has been in remission from BD. He has no depressive, motor, or non-motor symptoms. He has become socially active and is functioning very well. Figures 1 and 2 depict the course and management of BD, PD, and catatonia in this patient.

Figure 1 Clinical Timeline of symptoms and interventions. ECT: Electroconvulsive therapy.

Figure 2 Management of catatonia. ECT: Electroconvulsive therapy; BFCRS: Bush-Francis Catatonia Rating Scale; PHQ-9: Patient Health Questionnaire-nine item version; MMSE: Mini-mental State Examination.

FOCUSED REVIEW

Aim

Instead of a systematic review, this article includes a focused review of issues relevant to the assessment and management of the patient’s problems. These issues included the profile of non-motor symptoms in PD and psychiatric symptoms or disorders associated with PD, with a special focus on comorbid BD and PD. Other areas reviewed included differentiating the symptoms of PD and depression, and distinguishing drug-induced parkinsonism (DIP) from idiopathic PD. The review also included the occurrence of catatonia in PD and the use of ECT in PD.

Method

Search strategy: The databases searched included PubMed, Google (for grey literature), and the Reference Citation Analysis database. The period chosen was the year 2000, when literature on non-motor symptoms of PD began to emerge, to 2025. The search included combinations of the following terms: PD, non-motor symptoms, psychiatric symptoms, mania, BD, bipolar depression, catatonia, DIP, and ECT in PD.

Selection criteria: The focused review included all articles relevant to the areas mentioned above. These articles included case reports, case series, observational studies, treatment trials, narrative and systematic reviews, and meta-analyses. Articles not included were those not in English, animal studies, and media articles.

Data extraction: Demographic, clinical, and treatment information related to the areas mentioned were extracted and summarised.

Results

The focused search yielded 135 articles on the different aspects of non-motor symptoms of PD. These articles included reviews, meta-analyses, studies, and case reports.

Non-motor symptoms of PD: Supplementary Table 2 lists the various non-motor symptoms of PD and their characteristics. Non-motor symptoms are very common in PD[4-7]. Their prevalence ranges from 33% to 100% across different studies. Patients with PD experience a higher number of more severe non-motor symptoms compared to those without PD. The deposition of Lewy bodies in the gastrointestinal tract, olfactory structures, hypothalamus, and autonomic nervous system begins several years before the basal ganglia are affected. As a result, many non-motor symptoms appear years or even decades before motor dysfunction and the clinical diagnosis of PD. Notably, constipation, depression, anxiety, olfactory disturbances, sleep problems, including rapid eye movement sleep behaviour disorder, and autonomic disturbances may precede motor symptoms by decades. Non-motor symptoms can occur at any stage of PD[1,5-7]. For about 20% of patients, these symptoms may be the initial presentation of PD[7]. In advanced stages, non-motor symptoms often overshadow motor symptoms[1,7]. Their presence increases the risk of developing PD. Constipation and mood disorders can increase this risk by 2-4 times[1], while patients with rapid eye movement sleep behaviour disorder have a 33%-90% chance of eventually developing PD[5,15]. Treating non-motor symptoms can be challenging, especially in later stages of PD, which include motor symptoms resistant to dopaminergic medications, treatment complications, and a predominance of difficult-to-manage non-motor symptoms[1-3,7]. These symptoms negatively impact the course and outcomes of PD, leading to increased disability, impaired quality of life, higher mortality rates, early institutionalisation, increased healthcare costs, and greater caregiver burden.

Psychiatric symptoms or disorders associated with PD: Supplementary Table 3 describes the characteristics of these symptoms or disorders. Psychiatric symptoms and disorders are categorised into mood (depressive, anxiety), cognitive, thought and perceptual (hallucinations, psychosis), and motivational disorders (apathy, impulse control)[8]. Some of these symptoms, such as depression, anxiety, and apathy, result from the neurodegenerative processes of PD[9,10]. Neurodegeneration, as well as the use of dopaminergic medications, can cause psychotic symptoms. Impulse control disorders are more likely to be a direct consequence of dopaminergic medications. Psychiatric symptoms are similar to other non-motor symptoms in many respects. They are highly prevalent (50%-90%)[8,16]. About 45% of patients have multiple psychiatric disorders[17]. Both the prevalence and severity of psychiatric symptoms increase as PD progresses[8,9,12,16,18-23]. Depressive, anxiety, and psychotic disorders are present in 50%-70% patients with late-stage PD, while 83% of the patients have dementia after 20 years of the illness. Psychiatric symptoms also occur in the pre-motor stage of PD[3,7-10]. Depression and anxiety can precede motor dysfunction in 30% of patients with PD by 4-20 years[7,8,18,20,24]. Psychosis, BD, and subtle cognitive impairment are also known to occur in the pre-motor phase[3,7,18,20]. Depression, anxiety, cognitive deficits, and BD all increase the risk of developing PD by 2-4 times[3,24,20,25]. Depression, anxiety, psychosis, BD, and cognitive impairment are often associated with each other and also with non-motor symptoms such as sleep disturbances, fatigue, and olfactory dysfunction[7-9,26]. Finally, psychiatric symptoms are specifically associated with adverse outcomes, such as disability, poor quality of life, early institutionalisation, caregiver burden, higher costs and excess mortality[8,10,16,26,27].

BD and catatonia in PD: Among all the psychiatric disorders listed in Supplementary Table 3, BD has been the least studied condition. Nevertheless, a study found that 11% of patients hospitalised with PD had BD[28]. BD was three times more likely to be associated with PD compared to the general population controls, 5% of whom had BD in this study. BD is also known to precede motor symptoms of PD by several years[18]. The occurrence of BD and depressive symptoms during the pre-motor and motor phases of PD leads to poorer outcomes and greater disability[8,29]. Depressive episodes in PD are often characterised by co-occurring anxiety in 50%-80% of patients[3,30,31]. Depression is also associated with apathy, other non-motor symptoms, and more severe motor symptoms of PD[3,8,10,20]. Finally, BD increases the risk of developing PD by two to six times during the three to six-year period before diagnosis[25,29,32-34].

BD is linked to psychomotor abnormalities, including catatonia, while patients with PD exhibit motor symptoms that can resemble catatonia[35]. Moreover, in a clinical sample of 250 patients with BD and PD, 7% had catatonia compared to patients with only PD[29]. However, catatonia is considered a relatively rare psychiatric comorbidity of PD, and its documentation is mainly limited to case reports.

Other results: The next section presents the review findings on differentiating PD and depressive symptoms (Table 1), distinguishing DIP from idiopathic PD (Table 2), the existing research on catatonia in PD (Table 3), and the use of ECT in PD (Table 4).

Table 1 Differentiating depression from parkinsonian symptoms.

Clinical profile of depressive disorders in PD	Shared symptoms of depressive disorders and PD	Discriminating symptoms of depressive disorders and PD	Diagnosing depressive disorder in PD
Persistent and pervasive low mood, sadness, and tearfulness	Lowered mood	Motor features	Low mood, anhedonia, and apathy are the most sensitive indicators of depressive disorders in PD
Dysphoria, irritability	Anhedonia	Downcast look, low mood, reduced or preserved mood reactivity, and agitation in depressive disorder	Neurovegetative symptoms are less effective in distinguishing patients with PD with or without depressive disorders
Preserved mood reactivity	Apathy	Bradykinesia, rigidity, tremor, stooped posture, shuffling gait, and masked facies in PD[18]	The presence of typical melancholic symptoms may help differentiate patients with PD with or without depressive disorders
Anxiety and panic attacks	Diminished emotional expression - lack of facial expressions, flat mood	Psychomotor slowing	A focus on mood and cognitive symptoms rather than neurovegetative symptoms helps in the diagnosis of depressive disorder in PD[18,19]
Anhedonia - diminished enjoyment	Anxiety	Similarities between parkinsonian motor symptoms, psychomotor slowing, negative symptoms and depressive symptoms in major schizophrenia, depressive, and bipolar disorder are evident	An inclusive approach that takes into account neurovegetative symptoms regardless of their possible aetiology is recommended for the diagnosis of depressive disorder in PD[10,30]
Apathy - reduced interest, loss of initiative	Autonomic symptoms	Despite these similarities, motor symptoms of parkinsonism are not correlated with negative and depressive symptoms in schizophrenia and mood disorders	-
Pessimism	Loss of energy, fatigue, tiredness	Motor symptoms of PD are not strongly associated with psychomotor slowing in schizophrenia and mood disorders	The motoric state, wearing on or off, s should be considered while diagnosing depressive disorders in PD[15,31]
Hopelessness	Slowing and retardation	A total score of ≥ 4 on the Simpson-Angus Scale is a clinically meaningful and reliable method for distinguishing parkinsonian from depressive symptoms[35]	The presence of coexisting cognitive impairment should be noted[30]
Mental slowing	Loss of appetite, weight loss	-	-
Diminished concentration	Insomnia, hypersomnia	-	-
Memory impairment	Mental slowing	-	-
Loss of energy, fatigue, tiredness	Diminished concentration	-	-
Slowing and retardation	Memory impairment[7,9,10,19,30]	-	-
Mild symptom severity	-	-	-
Present during wearing-off periods	-	-	-
Relative absence of self-blame, guilt, reproach, and low self-esteem	-	-	-
Frequent suicidal ideations but very few suicide attempts	-	-	-
Relative lack of psychotic symptoms[3,18,19,36,37]	-	-	-

PD: Parkinson’s disease.

Table 2 Differentiating drug-induced and idiopathic Parkinson’s disease.

Clinical features and other characteristics	DIP	IPD
Cause	Blockade of dopamine D2 receptors. Temporal association with offending medications	Degeneration of nigrostriatal dopaminergic neurons
Sex distribution	More common in women	Slightly more common in men
Symmetry	Usually bilateral and symmetric features, but asymmetric features may be present in up to half of the patients	Unilateral and/or asymmetric features
Bradykinesia	More prominent	Present
Rigidity	More prominent	Present
Resting tremors	Relatively absent	Present
Coexistence of tardive dyskinesia	More common	Less common
Freezing gait	Relatively absent	Present
Olfactory dysfunction	Absent	Present in about 90% of the patients at any stage of IPD
Other non-motor symptoms	Absent	Sleep disturbance and urinary dysfunction may be present
Response to levodopa	Lack of response or a diminished response	Usually, a good response that is diagnostically useful
Dopamine transporter imaging by SPECT or PET	Medications causing parkinsonism, including antipsychotics, have negligible affinity for the transporter, so scans may demonstrate normal uptake even with significant DIP	Transporter uptake in the striatum is significantly decreased in patients with IPD, even in early stages of the disease
Resolution of symptoms	DIP usually resolves within months of stopping the offending drug, but unmasked PD may persist or progress in 10%-50% patients	Symptoms increase with time

PD: Parkinson’s disease; DIP: Drug-induced parkinsonism; IPD: Idiopathic Parkinson’s disease; SPECT: Single-photon emission computed tomography; PET: Positron emission tomography.

Table 3 Clinical profile of patients with Parkinson’s disease presenting with catatonia.

Patient reports
Ref.	Patient	Primary diagnosis	Catatonic features	Treatment	Outcome
Suzuki et al[49], 2006	62-year-old woman	PD with psychosis	Acute onset of catatonic excitement followed by stupor, features of neuroleptic malignant syndrome, probably induced by quetiapine	Quetiapine stopped, dantrolene for neuroleptic malignant syndrome, reinstatement of levodopa, and 12 ECT sessions	Marked improvement: Near-complete resolution of catatonia and psychiatric symptoms with ECT
Kamigaichi et al[50], 2009	75-year-old woman	PD with psychosis	Acute onset of catatonic stupor following withdrawal of some dopaminergic medications. Associated psychotic symptoms, but no features of neuroleptic malignant syndrome. No cognitive impairment	Increase in the dose of levodopa. Did not respond to benzodiazepines. Two ECT sessions	Complete resolution of catatonia with ECT
Poyraz et al[51], 2016	80-year-old woman	PD with psychosis	Past history of catatonic stupor. Acute onset of catatonic stupor associated with psychotic symptoms. Features of delirium	Partial response to benzodiazepines. Optimisation of anti-parkinsonian treatment and increase in the dose of levodopa. Six sessions of ECT once the patient was clinically stable	Improvement in catatonic symptoms with ECT, but residual catatonia and mild cognitive impairment persisted
Ramesh et al[52], 2019	55-year-old man	PD with psychosis	Acute onset of catatonic stupor following institution of quetiapine	Treatment with levodopa. Partial response to lorazepam. Six sessions of ECT	Complete resolution of catatonia and marked improvement in psychotic symptoms with ECT
Elefante et al[36], 2022	56 and 58-year-old women	PD with BD, type I and type II. Comorbid anxiety	Acute onset of catatonic stupor during depressive episodes with psychotic symptoms. No cognitive impairment	Antiparkinsonian medication. Poor response to lorazepam. Eight to fifteen ECT sessions	Complete resolution of catatonia with ECT
Longitudinal cohort study
Study	Patient sample	Prevalence of catatonia	Other features
Onofrj et al[29], 2021	Clinical cohort of 250 patients with BD and PD. Followed up at 3 and 6 years. BD preceded the onset of PD by several years	Seven per cent of the patients (n = 14) with BD and PD had catatonia. Prevalence was significantly greater than in patients with only PD (1%)	The prevalence of catatonia was considerably lower than that of depression, psychosis, and dementia. Two patients were carriers of GBA gene mutations

PD: Parkinson’s disease; BD: Bipolar disorder; ECT: Electroconvulsive therapy.

Table 4 Electroconvulsive therapy in Parkinson’s disease: Reviews and meta-analysis.

Acute ECT
Ref.	Study type	Key findings
Faber and Trimble[53], 1991	Narrative review of 27 studies, mostly case reports and uncontrolled studies with small samples; only one randomised-controlled trial; 20 studies included patients with comorbid depression	Approximately 50% of patients receiving ECT, irrespective of the presence or absence of psychiatric comorbidity, showed improvement in parkinsonian symptoms
Kennedy et al[54], 2003	Systematic review of 51 studies evaluating ECT in movement disorder	Significant improvement in both psychiatric and motor symptoms of Parkinson’s disease with ECT; however, significant side effects, particularly delirium (44%-85%), were reported
Borisovskaya et al[55], 2016	Systematic review of 43 studies of ECT in Parkinson’s disease with comorbid depression	Depression improved in 93% of patients; motor symptoms improved in 83%; up to 56% developed delirium, but no long-term cognitive impairment was observed in 94% of patients
Takamiya et al[56], 2021	Meta-analysis of 14 studies (including 1 randomised-controlled trial1) evaluating ECT in PD	ECT significantly improved motor manifestations of Parkinson’s disease; improvement was significant in patients without psychiatric symptoms; ECT also significantly improved depression and psychosis, relieved the wearing-off phenomenon, and did not worsen cognitive functioning
Maintenance ECT
Kramer et al[57], 1999	Major depressive disorder (n = 24)	Major depressive disorder with PD (n = 10)
	Much improved 75%	Much improved 50%
	Partially improved 12.5%	Partially improved 40%

¹The only randomised-controlled trial of active vs sham electroconvulsive therapy was conducted by Andersen et al[58]. In 11 patients with Parkinson’s disease, electroconvulsive therapy improved motor symptoms and the wearing-off phenomenon, but the effects were short-lasting.

PD: Parkinson’s disease; ECT: Electroconvulsive therapy.

DISCUSSION

What does this patient report add to the existing literature?

The final diagnoses for this patient were type II BD, with the most recent episode being depression, idiopathic PD, and catatonia secondary to PD. Although the hypomanic episodes occurred while he was taking antidepressants, the duration of 2-3 months indicated spontaneous hypomania rather than being induced by antidepressants. The current depressive episode was severe, persistent (lasting more than 2 years), and associated with significant functional impairment, treatment non-response, prominent anxiety symptoms, and apathy. Remarkably, the symptoms of BD had preceded parkinsonian symptoms by over 30 years. Parkinsonian symptoms only became evident during the index episode and rapidly progressed to severe motor dysfunction. Non-motor symptoms, such as urinary incontinence and constipation, were also present during this depressive episode.

Thus, this patient’s presentation illustrated the features typical of comorbid BD and PD. BD is known to precede motor symptoms of PD by several years[8,18,29]. Bipolar depression during the pre-motor and motor phases of PD is associated with more severe motor symptoms and leads to poorer outcomes and greater disability. Depressive episodes in PD are often characterised by co-occurring anxiety in 50%-80% of patients[3,30,31], apathy, and other non-motor symptoms of PD[3,8,10,20]. Finally, BD increases the risk of developing PD by two to six times during the three to six years before diagnosis[25,29,32-34]. Whether BD contributed to the development of PD in this patient remains an intriguing possibility.

Comorbid BD and PD with catatonia is a rare occurrence. The only longitudinal study on this subject found that the prevalence of catatonic symptoms in comorbid BD and PD was much lower than that of depression, psychosis, dementia, and somatic disorders[29]. Only two patients with BD and catatonia have been reported[36]. In both women, the interval between the onset of BD and PD was relatively short. There were some features of delirium, but the reports do not mention other non-motor symptoms. The patients received ECT after a delay. Although the catatonia resolved, the PD motor symptoms did not improve as much. These studies did not report long-term follow-up. In contrast, our patient had a more than 30-year gap between the onset of BD and PD. Non-motor symptoms, such as anxiety, apathy, urinary incontinence, and constipation, were present. Nevertheless, the previous psychiatrist missed the diagnosis of PD because of the overlap with depression and DIP. There was no delay in starting ECT in this patient. In addition to resolving catatonia, ECT led to marked improvement in motor and non-motor symptoms of PD. The patient maintained this improvement with continuation ECT and appropriate continuation pharmacotherapy for more than 18 months.

The clinical presentation suggests that the diagnosis of PD can be missed in these complex, comorbid conditions unless there is a high index of suspicion for PD, and psychiatrists conduct appropriate assessments in close collaboration with neurologists. Early initiation of ECT is highly effective in resolving catatonia and improving PD symptoms. Despite the poor prognosis of this comorbidity, it may be possible to sustain clinical and functional recovery with appropriate maintenance treatment.

Under-recognition of PD in patients with comorbid psychiatric disorders

In this patient, parkinsonian symptoms became evident during the most recent depressive episode. However, the previous psychiatrist had missed the diagnosis of PD. The common reasons for under-recognition of PD during depressive episodes are the overlap of depressive and parkinsonian symptoms and the attribution of motor symptoms to medications used to treat BD.

Overlap of motor symptoms of PD and depression: Table 1[37,38] lists the overlapping and distinguishing symptoms of depression in PD.

Depressive disorders are usually mild and include all typical symptoms. Anxiety, dysphoria, apathy, anhedonia, and irritability are especially common, while psychotic symptoms, self-blame, reproach, guilt, and suicidal attempts are rare[3,18,19,37,38]. However, many of these symptoms are common in patients with PD without depression[7,9,10,19,30]. Therefore, the only distinguishing feature is the presence of classic motor symptoms of PD[18,35]. A network meta-analysis by Fritze et al[35] found similarities between motor symptoms of PD, psychomotor retardation, and negative and depressive symptoms of schizophrenia and mood disorders. However, the motor symptoms were not strongly associated with psychomotor retardation or negative and depressive symptoms. The authors concluded that a total cut-off score of ≥ 4 on the Simpson-Angus Scale was a clinically meaningful and reliable way of distinguishing parkinsonian from depressive symptoms.

The important role of motor symptoms in differentiating depression from PD suggests that patients with depression, especially older patients, should be carefully examined for motor symptoms of PD. Typically, a consultation with neurologists is necessary to confirm the diagnosis of PD. When the diagnosis is uncertain, a SPECT (single-photon emission computed tomography) or positron emission tomography scan to assess dopamine transporter uptake can be helpful[2].

Overlap between drug-induced and idiopathic PD: Psychiatrists often miss idiopathic PD in the presence of comorbid psychiatric disorders because of difficulties in distinguishing DIP from idiopathic PD. In the general population, especially among older adults, DIP is the second most common cause of parkinsonism after idiopathic PD[39-43]. Clinicians have to distinguish three entities: DIP (parkinsonism related to medications), medication exposure unmasking an underlying or latent Parkinsonism, and idiopathic PD. DIP occurs in 30%-40% of patients on antipsychotics. Both first- and second-generation medications can cause DIP. DIP also occurs with antiemetic agents, antidepressants, lithium, and calcium channel blockers. There is a significant individual variability in the propensity to develop DIP, partially explained by genetic polymorphisms.

Table 2[39-43] shows the distinguishing characteristics of DIP and idiopathic PD. The distinction between DIP and PD may be difficult in the early stage of PD. It is even more difficult for patients with latent PD unmasked by medications. Dopamine transporter imaging is the only reliable way to distinguish the 3 patient groups.

Possibility of quetiapine-induced catatonia in PD

The cause of the patient’s catatonia was uncertain. Catatonia could have been part of BD. However, the depressive symptoms had mostly improved, and the remaining symptoms could not explain the sudden development of a severe catatonic syndrome. Quetiapine was started in this patient because of its established efficacy for bipolar depression[44]. Apart from clozapine, quetiapine, especially at low doses, is the only antipsychotic least likely to worsen motor symptoms of PD[39,43,45].

Nevertheless, the onset of catatonia quickly followed quetiapine treatment at a relatively low dose of 75 mg/day. The Naranjo Adverse Drug Reaction Probability Scale score was 4, indicating a possible relationship based on the onset of catatonia following quetiapine, which is a known side effect of quetiapine and not part of PD[46]. However, catatonia is very rarely induced by quetiapine[47,48]. The higher selectivity of quetiapine for 5-hydroxytryptamine receptor type 2 receptors than for D2 receptors makes it less likely to cause catatonia[43,47]. Nevertheless, quetiapine may induce catatonia by dopamine blockade that is not compensated for by γ-aminobutyric acid (GABA) inhibition[48]. The catatonia lasted over a week after stopping quetiapine and did not respond to lorazepam. Therefore, secondary catatonia due to PD appeared to be the most likely explanation.

Catatonia in PD

Table 3 summarises existing research on catatonia in PD[29,36,49-52]. Patient reports frequently describe catatonia among individuals with PD and chronic psychotic disorders. Only two patients with BD and catatonia have been reported[36]. A longitudinal study found that catatonia is rare in patients with both BD and PD[29]. Although the prevalence of catatonia (7%) was significantly higher in patients with comorbid BD and PD compared to those with only PD, it was still less common than depression, psychosis, and dementia. Based on patient reports, catatonia in the context of PD with either psychosis or BD shared several features with this patient’s presentation. Almost all the patients were older persons. The most common presentation was catatonic stupor. In two cases, catatonia followed treatment with quetiapine. Although two patients experienced delirium and symptoms suggestive of neuroleptic malignant syndrome during the acute phases, cognitive impairment was minimal or absent. The patients only partially responded to lorazepam treatment. Conversely, these reports found significant improvement or complete resolution of catatonia and other psychiatric symptoms in all patients treated with ECT. These patient reports, and the present one, suggest that catatonia in comorbid BD and PD may respond incompletely to benzodiazepines, while ECT appears associated with significant improvement. However, the evidence remains limited to patient reports and cannot be deemed conclusive.

ECT in PD

Table 4 presents the evidence for ECT in PD[53-58]. The evidence is limited, but acute ECT improves motor symptoms in 59%-90% of patients with PD. Depressive symptoms also improve in most patients. Although the reviews have found delirium in 44%-85% of patients with acute ECT, long-term cognitive impairments are rare. About 7-8 uncontrolled studies have reported the efficacy of continuation or maintenance ECT in PD[49,50]. However, ECT is not a viable treatment for PD due to the lack of controlled evidence, short-lived effects, and high rates of side effects[30,37,54,59].

Comorbid BD and PD with catatonia: Possible biological substrates

Shared mechanisms involving the cortico-striato-thalamocortical (CSTC) circuits and the GABAergic system can explain this patient’s presentation and management. Dopamine depletion in the CSTC circuits, including the motor, cognitive, and limbic loops, can cause motor and non-motor mood symptoms in PD[60]. Reduced GABAergic transmission associated with dopamine in PD can also lead to motor and non-motor symptoms[61,62]. In PD, motor impairments, such as gait abnormalities and postural instability, and non-motor symptoms, such as depression and anxiety, are particularly linked to GABA-A receptor hypofunction[61,62]. Abnormalities of the direct and indirect CSTC pathways, GABAergic dysfunction, and GABA-A receptor hypofunction are similarly implicated in BD[63,64]. Lastly, in catatonia, the breakdown of CSTC circuits prevents the integration of the salience, default mode, and executive function networks[65]. The GABA hypothesis of catatonia proposes that GABA-A receptor hypofunction causes catatonia, while GABA-B receptor hyperfunction worsens catatonia[66].

Benzodiazepines like lorazepam act at the GABA-A receptors to promote the inhibitory GABAergic tone[58,67]. This mechanism explains lorazepam’s efficacy in treating catatonia. Therefore, the loss of GABA-A receptors in PD, BD, and catatonia may interfere with lorazepam’s positive effects in catatonia. In contrast, ECT has a broader spectrum of action, including anticonvulsant efficacy through enhanced GABAergic function, neurogenesis via potentiation of brain-derived and vascular endothelial growth factors, and enhancing hippocampal neuroplasticity[68]. Therefore, ECT is likely to modulate GABAergic tone in CSTC circuits more effectively, which may explain its enhanced efficacy in patients with comorbid BD and PD who develop catatonia.

Limitations and future directions

The existing literature on psychiatric disorders in PD has rarely examined the occurrence of BD. The occurrence of catatonia in comorbid BD and PD, and the efficacy of ECT in this complex presentation, is based on only a few patient reports. Therefore, further research is essential to provide better insights regarding comorbid BD and PD with catatonia. Future research regarding BD and catatonia associated with PD should include larger, longitudinal studies, properly designed treatment trials, and investigations of underlying genetic, structural and functional mechanisms.

CONCLUSION

In summary, the clinical presentation of this patient shows that, although BD and catatonia are rare in PD, both are serious and disabling comorbid conditions. BD typically develops several years before PD and can negatively influence the prognosis of PD. Catatonia occurs during treatment-resistant depressive episodes of comorbid BD and PD. In the complex setting of comorbid BD and PD, catatonia may prove refractory to benzodiazepine treatment. However, ECT can lead to rapid resolution of catatonia, together with significant and sustained improvement in both refractory depression and motor symptoms of PD. The underlying neurobiological mechanisms could involve GABAergic dysfunction in the CSTC circuits.

Non-motor symptoms of PD, including psychiatric disorders, are often overlooked and undertreated. Maintaining a high index of suspicion for psychiatric symptoms and screening patients with PD for these issues can help prevent this oversight. Digital tools to detect and monitor non-motor symptoms of PD may improve their detection[69]. Conversely, patients with psychiatric disorders, especially older ones, should be carefully examined for motor symptoms of PD. Finally, close collaboration between psychiatrists and neurologists is essential for early detection and effective management of PD in patients with psychiatric disorders.

ACKNOWLEDGEMENTS

We are grateful to the patient and his family for allowing us to present the details of his illness.